Kidney function and cognitive and physical decline in older women

老年女性的肾功能以及认知和身体衰退

• 批准号: 7581040
• 负责人: JULIE LIN
• 金额: $ 35万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7581040
• 关键词: Aging; Albumins; Albuminuria; Biological Assay; Biological Markers; Blood; Blood Vessels; Bone Diseases; Brain; C-reactive protein; Chronic Kidney Failure; Cognitive; Communities; Creatinine; Data; Diabetic Angiopathies; Disease; Elderly; Epidemic; Etiology; Fibrinogen; Frequencies; Functional disorder; Glomerular Filtration Rate; Growth; Health; Healthcare; Impaired cognition; Individual; Inflammation; Inflammatory; Investigation; Kidney; Kidney Diseases; Kidney Failure; Life Style; Link; Longevity; Measurement; Measures; Mediating; Mediator of activation protein; Medical; Metabolism; Microalbuminuria; Minerals; Modeling; Morbidity - disease rate; Muscle; Nurses' Health Study; Outcome Measure; Participant; Physical Function; Plasma; Population; Prevalence; Prospective Studies; Public Health; Quality of life; Questionnaires; Receptors, Tumor Necrosis Factor, Type II; Renal function; Reporting; Research Infrastructure; Resources; Risk; Role; SF-36; Sampling; Spottings; TNFR-Fc fusion protein; Testing; Time; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; United States; Uremia; Urine; Vascular Diseases; Walking; Woman; Work; aged; aging population; clinical care; cognitive function; cohort; cost; falls; follow-up; functional decline; improved; inflammatory marker; innovation; mortality; neuromuscular; older women; population based; primary outcome; receptor; urinary; vascular inflammation

DESCRIPTION (provided by applicant): Progressive cognitive and physical function decline in the aging population in the United States requires a substantial allocation of healthcare resources. Aging is also associated with increased prevalence of chronic kidney disease. Advanced kidney failure is an important etiology of cognitive and physical dysfunction, likely mediated through vascular disease, abnormal mineral metabolism, and neuromuscular degeneration, but sparse data are available concerning the role of mild and moderate kidney failure. We hypothesize that mild and moderate chronic kidney disease will be independently associated with cognitive and physical decline in older adults. This prospective study will include 3700 community-dwelling women participating in the Nurses' Health Study who are aged 70 and older, have stored plasma from 1989 and 2000, stored urine from 2000, and who have undergone repeated cognitive function testing every two years. Physical function is assessed every four years by the physical component score of the Short Form-36, walking pace, and frequency of falls as reported on the questionnaires. Our measurements of cognitive and physical functioning have been validated as significant predictors of morbidity and mortality in population-based studies of older adults. We will assay plasma for creatinine, which will allow us to estimate GFR, and urine for microalbuminuria. A growth curve approach to multivariable modeling to test for associations between kidney dysfunction and subsequent 1) cognitive or 2) physical function decline will allow us to take advantage of multiple repeated measures of these outcomes obtained between 2000 and 2008. Specific aims of this proposal include evaluating how 1) baseline eGFR in 2000, 2) >25% eGFR decline between 1989 and 2000 (over 11 years), and 3) presence of microalbuminuria are related to cognitive and physical decline between 2000 and 2008 (over 8 years). We will also investigate whether inflammatory biomarkers, namely C- reactive protein, fibrinogen, and tumor necrosis factor a receptor-2, may potentially mediate associations between kidney dysfunction and functional decline. We will have >80% power for our aims. Completed and on-going work in this established cohort make this project extremely cost-effective. From a public health perspective, recognition of these associations may result in improving clinical care for the geriatric population through medical management strategies that slow progression of early and moderate kidney disease, cognitive impairment, and physical function decline. Thus, findings from this longitudinal, prospective study of a large cohort of older women will meaningfully improve the quality of life and longevity of community-dwelling older citizens.

描述（由申请人提供）：美国人口老龄化导致认知和身体功能逐渐下降，需要大量的医疗资源分配。衰老还与慢性肾病患病率增加有关。晚期肾衰竭是认知和身体功能障碍的重要病因，可能是通过血管疾病、矿物质代谢异常和神经肌肉变性介导的，但关于轻度和中度肾衰竭的作用的数据很少。我们假设轻度和中度慢性肾脏疾病与老年人的认知和身体衰退独立相关。这项前瞻性研究将包括 3700 名参与护士健康研究的社区居住女性，她们年龄在 70 岁及以上，储存过 1989 年和 2000 年的血浆，储存过 2000 年的尿液，并且每两年接受一次重复的认知功能测试。每四年根据问卷中报告的 Short Form-36 身体成分评分、步行速度和跌倒频率对身体功能进行评估。在基于人群的老年人研究中，我们对认知和身体功能的测量已被验证为发病率和死亡率的重要预测因素。我们将检测血浆中的肌酐，这将使我们能够估计 GFR，并检测尿液中的微量白蛋白尿。采用多变量建模的生长曲线方法来测试肾功能障碍与随后的 1) 认知或 2) 身体功能下降之间的关联，这将使我们能够利用 2000 年至 2008 年间获得的这些结果的多次重复测量。该提案的具体目标包括评估 1) 2000 年的基线 eGFR，2) 1989 年至 2000 年（超过 11 年）期间 eGFR 下降 >25%，以及 3) 是否存在2000 年至 2008 年（超过 8 年）期间，微量白蛋白尿与认知和身体衰退有关。我们还将研究炎症生物标志物，即 C 反应蛋白、纤维蛋白原和肿瘤坏死因子 a 受体 2，是否可能介导肾功能障碍和功能衰退之间的关联。我们将拥有超过 80% 的力量来实现我们的目标。这个既定团队中已完成和正在进行的工作使该项目极具成本效益。从公共卫生的角度来看，对这些关联的认识可能会通过减缓早期和中度肾脏疾病、认知障碍和身体功能下降的进展的医疗管理策略来改善老年人群的临床护理。因此，这项针对大量老年妇女的纵向前瞻性研究的结果将有意义地改善社区老年公民的生活质量和寿命。